The addition of DTPA to [177Lu-DOTA0,Tyr3]octreotate prior to administration reduces rat skeleton uptake of radioactivity

Peptide receptor-targeted radionuclide therapy is nowadays also being performed with DOTA-conjugated peptides, such as [DOTA(0),Tyr(3)]octreotate, labelled with radionuclides like Lu-177. The incorporation of Lu-177 is typically greater than or equal to99.5%; however, since a total patient dose can be as high as 800 mCi, the amount of free Lu-177(3+) (= non-DOTA-incorporated) can be substantial. Free Lu-177(3+) accumulates in bone with unwanted irradiation of bone marrow as a consequence. Lu-177-DTPA is reported to be stable in serum in vitro, and in vivo it has rapid renal excretion. Transforming free Lu3+ to Lu-DTPA might reroute this fraction from accumulation in bone to renal clearance. We therefore investigated: (a) the biodistribution in rats of (LuCl3)-Lu-177, [Lu-177-DOTA(0),Tyr(3)]octreotate and Lu-177-DTPA; (b) the possibilities of complexing the free Lu-177(3+) in [Lu-177-DOTA(0),Tyr(3)]octreotate to Lu-177-DTPA prior to intravenous injection; and (c) the effects of free Lu-177(3+) in [Lu-177-DOTA(0),Tyr(3)]octreotate, in the presence and absence of DTPA, on the biodistribution in rats. (LuCl3)-Lu-177 had high skeletal uptake (i.e. 5% ID per gram femur, with localization mainly in the epiphyseal plates) and a 24-h total body retention of 80% injected dose (ID). [Lu-177-DOTA(0),Tyr(3)]octreotate had high and specific uptake in somatostatin receptor-positive tissues, and 24-h total body retention of 19% ID. Lu-177-DTPA had rapid renal clearance, and 24-h total body retention of 4% ID. Free Lu-177(3+) in [Lu-177-DOTA(0),Tyr(3)]octreotate could be complexed to Lu-177-DTPA. Accumulation of Lu-177 in femur, blood, liver and spleen showed a dose relation to the amount of free Lu-177(3+), while these accumulations could be normalized by the addition of DTPA. After labelling [DOTA(0),Tyr(3)]octreotate with Lu-177 the addition of DTPA prior to intravenous administration of [Lu-177-DOTA(0),Tyr(3)]octreotate is strongly recommended.